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The 2008 CNRS Gold Medal, the highest scientific research award in France, has been awarded to internationally renowned geneticist Jean Weissenbach, senior researcher at CNRS. Weissenbach, 62, developed the first high-resolution genetic map of the human genome. Thanks to this tool, used as a reference in the field, hundreds of genes linked to genetic diseases have been discovered, making early diagnosis possible. Weissenbach also participated in the ambitious human genome sequencing project and the development of innovative techniques for exploring the genomes of biology's model organisms (fruit fly, rice, etc.). Since 1997, he has been the director of Genoscope-Centre national de séquençage (CEA) and the Joint Research Unit “Génomique métabolique” (Université d'Evry/CNRS/CEA), both of which are located on the Genopole campus. In the past few years, he has reoriented research in his laboratory toward the study of microorganisms in ecosystems, which are a source of essential biocatalysts for the chemistry of the future.

After doing research in molecular biology in his hometown of Strasbourg in the 1970s, Weissenbach started to work on human interferon(1)genes(2) . At the Institut Pasteur in Paris, he familiarized himself with the still-recent recombinant DNA(3)techniques that make it possible to clone DNA fragments and isolate genes. This led him to human molecular genetics, which has been his research field since 1981. His work mainly focuses on the sex chromosomes. His team succeeded, notably, in producing the first map of the Y chromosome and identifying the segment of DNA containing the gene encoding the male sex determining factor.

A map for locating disease genes

How can “the” gene responsible for a given genetic disease be found within the vast territory of the human genome(4) ? This is a question that Weissenbach started focusing on in the 1990s. He thought the solution could be found by developing a detailed genetic map, in other words, identifying a collection of short sequences of DNA, called markers, each occupying a unique position on one of the chromosomes. These genetic markers make it possible to find one’s way around the genome and to locate disease genes. Their transmission through the generations can be followed, as the markers present small, distinguishing differences from one individual to another. Weissenbach, among others,thought that microsatellites(5)could represent ideal markers.

To see this mapping project through successfully, in the 1990s he helped create Généthon, funded entirely by the French Association Against Myopathies (AFM) and directed by Bernard Barataud. Within two years, Weissenbach had assembled a team, trained it, and obtained a promising initial map. Four years later, more that 5000 markers had been located, constituting the first high-resolution genetic map.

Immediately, teams from around the world started using this map that made it possible to locate within just a few months genes responsible for genetic diseases. Around 700 genes were discovered, including some by Weissenbach’s team. These discoveries were an important first step to be able to develop prenatal diagnostic tests. To study the offending genes and deepen understanding of the diseases, it was then necessary to have access to the gene’s sequence and mutations. This process would remain very laborious until the entire human genome was sequenced.

A sequence for further research

In 1997, Weissenbach was appointed director of the Genoscope, which he got up and running. The Genoscope joined the international public consortium that, despite initial competition from the private sector, was the only one to succeed in completely sequencing the human genome, accomplished in 2003. The next step was to locate genes within this sequence. Weissenbach’s team used a technique that compared the genetic sequence of the puffer fish with the human sequence to identify regions preserved over the course of evolution which, most often, contain genes. This allowed him to make the first realistic estimate of the number of genes in the human genome.

Genome sequencing for a number of other organisms would follow: Arabidopsis (a model plant), Anopheles (a malaria vector mosquito), rice, Paramecium (a unicellular model organism), the grapevine, and also unknown bacteria impossible to culture in the laboratory. Indeed, Weissenbach is persuaded that the biodiversity of microorganisms has an incredible amount to teach us and he has made them the priority at the Genoscope. His team studies, in particular, bacterial communities that live in sludge, with the goal of identifying new enzyme activities that could be useful to the chemical industry.

Weissenbach has been awarded a number of prizes for his work on genomes, including the CNRS silver medal in 1994 and the Grand Prix from the Foundation for Medical Research in 2007. He is also member of the FrenchAcademy of Sciences and several international academic organizations, such as the European Molecular Biology Organization (EMBO) and the Human Genome Organization (HUGO).

Notes:

1] Interferons are proteins involved in defending an organism against disease.
2] Genes are DNA fragments containing all the information necessary to produce RNA or, most often, a protein. One gene corresponds to one set of instructions to be carried out by the cell.
3] DNA is the basic molecule of genetic information, made of a succession of elementary chains called “nucleotides.”
4] A genome is an organism's complete genetic information, contained in chromosomes in each of its cells. The information in the genome is encoded in DNA.
5] Microsatellites are DNA sequences that have a short sequence of repeated chains (ACACACAC). These sequences are common, spread evenly throughout the entire genome, and have a variable length, depending on the individual (polymorphism).